Merck Announces Presentation of Interim Data from Study Evaluating
Lambrolizumab, an Investigational Anti-PD-1 Antibody, in Patients with
Advanced Melanoma at ASCO 2013
-Merck Expands Lambrolizumab Clinical Development Program-
-Study Published Online in the New England Journal of Medicine-
Business Wire
WHITEHOUSE STATION, N.J. -- June 2, 2013
Merck (NYSE: MRK), known as MSD outside the United States and Canada, today
announced the presentation of preliminary results from an ongoing Phase IB
expansion study evaluating the safety and efficacy of lambrolizumab (MK-3475),
Merck’s investigational antibody therapy targeting PD-1, in patients with
advanced (inoperable and metastatic) melanoma. The data were presented by
Antoni Ribas, M.D., Ph.D., professor, Hematology/Oncology and Surgery, and
director of the Tumor Immunology Program at the Jonsson Comprehensive Cancer
Center, University of California, Los Angeles, during an oral session at the
American Society of Clinical Oncology (ASCO) 2013 Annual Meeting in Chicago
(Abstract# 9009). The study was also published online in the New England
Journal of Medicine.
“We are encouraged by the results observed to date, including the rate and
duration of responses, in patients with advanced melanoma,” said Roger M.
Perlmutter, M.D. Ph.D., president, Merck Research Laboratories. “Based on
these data and additional findings from our ongoing studies, Merck plans to
initiate late-stage clinical trials of lambrolizumab in advanced melanoma, and
non-small cell lung cancer in the third quarter of 2013.”
Data from the ongoing multi-center, single-arm open-label Phase IB trial were
presented from 135 patients with advanced melanoma enrolled in the study and
who were administered an initial dose of lambrolizumab between Dec. 1, 2011,
and Sept. 6, 2012. Patients received one of three dosing regimens of
lambrolizumab (10mg/kg every two weeks [10mg/kg Q2W]; 10mg/kg every three
weeks [10mg/kg Q3W] or 2mg/kg every three weeks [2mg/kg Q3W]) until disease
progression or unacceptable toxicity. Tumor response was assessed every 12
weeks by independent, central, blinded radiographic review per RECIST 1.1
(Response Evaluation Criteria in Solid Tumors) criteria as well as
investigator-assessed, immune-related response criteria. Earlier interim data
from this study were presented at the 9th International Congress of the
Society for Melanoma Research (SMR) in Hollywood, Calif., in November 2012.
Objective response rates for lambrolizumab in patients with advanced melanoma
irRC Investigator RECIST 1.1 Independent Review
Assessment
^1ORR % Response ^1ORR %
Dose (95% CI) Duration (95% CI)
N N (mths)
10mg/kg Q2W 57 56 (42-69) 52 1.9+-10.8+ 52 (38-66)
10mg/kg Q3W 56 27 (16-40) 45 2.6 -8.3+ 27 (15-42)
2mg/kg Q3W 22 14 (3-35) 20 2.1+-5.5+ 25 (9-49)
Total 135 37 (29-45) 117 1.9+-10.8+ 38 (25-44)
^1 Objective response rate = confirmed complete response (CR) and partial
response (PR)
The interim overall confirmed response rate for lambrolizumab treatment was 38
percent (range 25–44 percent), as measured by RECIST 1.1 independent review
across all dosing regimens evaluated. The highest overall response rate
observed was 52 percent, which occurred in the 10 mg/kg Q2W dosing regimen.
Ten percent of patients in this dose group were complete responders. The
duration of confirmed responses, as measured after the first 12 week
evaluation, ranged from greater than 28 days to up to more than 8 months at
the time of the analysis, with 80 percent of responding patients continuing on
treatment. The median duration of response has not been reached with a median
follow-up time of 11 months. The most common treatment-related adverse events
observed for those patients evaluable for adverse events, as of December 2012,
were mostly grade 1/2 and included fatigue (30%), rash (21%), pruritus (21%)
and diarrhea (20%). Six (4.4%) treatment-related cases of pneumonitis were
reported (all grade 1/2). A total of 17 (13%) grade 3/4 treatment-related
adverse events were reported, the most common of these were fatigue (1.5%),
rash (2%) and elevated AST levels (1.5%). The majority of reported grade 3/4
events occurred in patients administered 10mg/kg Q2W.
The response rates for ipilimumab-pretreated and ipilimumab-naïve patients
treated with lambrolizumab were similar.
“We continue to make significant progress in our clinical development program
for lambrolizumab in multiple indications,” said Gary Gilliland, M.D., Ph.D.,
senior vice president and oncology franchise head, Merck Research
Laboratories. “We are very grateful to the patients, investigators, regulators
and the broader oncology community for their ongoing collaboration and support
in advancing this program.”
Lambrolizumab Clinical Development Program
Merck is currently conducting four clinical trials evaluating lambrolizumab in
multiple cancer types that involve more than 600 patients. The company
recently initiated a global, randomized, Phase II clinical trial of
lambrolizumab versus standard chemotherapy for patients with advanced melanoma
whose disease has progressed after prior therapy (ref: NCT01704287) and a
Phase I trial of lambrolizumab for the treatment of triple negative breast,
metastatic bladder cancer and head & neck cancer (ref: NCT01848834). Further
late-stage studies including a Phase III study evaluating lambrolizumab in
ipilimumab-naïve patients with advanced melanoma and a Phase II/III trial in
non-small cell lung cancer (NSCLC) are scheduled to commence in the third
quarter of 2013. Additional trials in several hematological cancers and
evaluation of lambrolizumab-containing combinations are scheduled to start
this year. Merck announced that lambrolizumab had received Breakthrough
Therapy designation from the U.S. Food and Drug Administration for advanced
melanoma in April 2013.
Merck Oncology Briefing Webcast
Merck will hold a briefing on June 2 at 1:00 p.m. CDT to present an update of
ongoing progress in the development of its oncology candidates MK-1775 and
vintafolide, as well as provide details regarding its clinical development
plans for lambrolizumab. Investorsand journalists may access a live audio
webcast of the event on Merck’s website at
http://www.merck.com/investors/events-and-presentations/home.html. Software
needed to listen to the webcast is available on the corporate website and
should be downloaded prior to the beginning of the webcast. A replay of the
webcast will be available at approximately 8:00 a.m. EDT on June 3.
About Lambrolizumab
Lambrolizumab is an investigational antibody therapy designed to disrupt the
action of the immune checkpoint protein PD-1 and therefore inhibit the ability
of some cancers to evade the body’s immune system. Lambrolizumab is being
studied in multiple cancer types including melanoma and non-small cell lung
cancer. For further details, please visit http://clinicaltrials.gov.
About Breakthrough Therapy Designation
The designation of an investigational drug as a Breakthrough Therapy is
intended to expedite the development and review of a candidate that is planned
for use, alone or in combination, to treat a serious or life-threatening
disease or condition when preliminary clinical evidence indicates that the
drug may demonstrate substantial improvement over existing therapies on one or
more clinically significant endpoints. The Food and Drug Administration Safety
and Innovation Act (FDASIA) includes a provision that allows sponsors to
request that an investigational drug be designated as a Breakthrough Therapy.
The implications of Breakthrough Therapy Designation cannot be determined at
this time.
About PD-1
Researchers have shown that several tumor types are able to hide in plain
sight by establishing a “molecular camouflage” that deceives the body’s immune
system into thinking they are normal and therefore allow them to grow
unchecked. The interaction between the immune checkpoint receptor PD-1 and its
ligands represents a potentially important tumor-specific immunomodulatory
mechanism. By utilizing the PD-1 pathway, a tumor cell can prevent the
activation of T-cells and therefore may block a key step that triggers the
immune system.
About Advanced Melanoma
Advanced melanoma accounts for more than 80 percent of skin cancer-related
deaths and one to two percent of all cancer deaths in the United States.
According to the American Cancer Society, an estimated 9,180 people in the
U.S. died from advanced melanoma in 2012.
About Merck
Today's Merck is a global healthcare leader working to help the world be well.
Merck is known as MSD outside the United States and Canada. Through our
prescription medicines, vaccines, biologic therapies, and consumer care and
animal health products, we work with customers and operate in more than 140
countries to deliver innovative health solutions. We also demonstrate our
commitment to increasing access to healthcare through far-reaching policies,
programs and partnerships. For more information, visit www.merck.com and
connect with us on Twitter, Facebook and YouTube.
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